The present invention relates to the use of selective dopamine D3 receptor ligands for the production of drugs for treating renal function disorders.
The present invention relates to the use of selective dopamine D3 receptor ligands for the production of drugs for treating renal function disorders.
Preferred receptor ligands are receptor antagonists.
In particular, the invention relates to drugs for the treatment of renal function disorders in which a disorder of the glomerular filtration rate in the sense of glomerular hyperfiltration occurs.
It is regarded as proven that the dopamine D3 receptor is expressed in the kidney, in particular in the nephron (cf. D. P. O'Connell et al., Hypertension, 1998, 32, 886).
It is regarded as proven that the dopamine D3 receptor is expressed in the kidney, in particular in the nephron (cf. D. P. O'Connell et al., Hypertension, 1998, 32, 886).
DE-A 4223921 very generally describes the use of dopamine receptor antagonists, without indication of specific subtypes, in the therapy of the progressive worsening of kidney function.
In Naunyn-Schmiedeberg's Arch. Pharmacol (1998) 358:690-693, G. Luippold et al. describe investigations with respect to the influence of specific D2 and D3 receptor antagonists on the renal hemodynamics and excretion function in a purely artificial functional state without pathophysiological changes.
L. D. Asico et al., J. Clin. Invest., Vol. 102 (1998), 493-498, describe that blockade of the D3 receptor results in increased renin production, renal sodium retention and, as a result, renin-dependent hypertension.
Sclerosing processes in the glomerular capillaries and disorders of the filtration rate caused thereby occur in disorders such as diabetes mellitus, hypertension, infectious or noninfectious glomerulonephritis, ascending urinary tract infections, sickle cell anemia, or compensatory hypertrophy after unilateral kidney resection.
The progressive worsening of the kidney function relates to nearly all patients with glomerulonephritis and more than one third of all patients with diabetes mellitus.
Kidney functional disorders occur as a result of glomerulosclerosis, which is also described as diabetic nephropathy, which is characterized histologically by a diffuse thickening of the glomerular capillaries and an alteration of the mesangium as a result of diffuse intercalation of basal membrane-like material or spherical fibrinous intercalations. As a result, an alteration of the filtration action occurs in the sense of hyperfiltration.
In glomerulonephritis too, a change in the glomerular basal membranes occurs and, as a result, a disorder of the filtration rate.